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Alpha Helix

The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform

Andrew D Hamilton – 1st expert on this subject based on the ideXlab platform

  • AlphaHelix mimetics as inhibitors of protein-protein interactions.
    Biochemical Society transactions, 2020
    Co-Authors: Ishu Saraogi, Andrew D Hamilton

    Abstract:

    The inhibition of protein-protein interactions using small molecules is a viable approach for the treatment of a range of pathological conditions that result from a malfunctioning of these interactions. Our strategy for the design of such agents involves the mimicry of side-chain residues on one face of the AlphaHelix; these residues frequently play a key role in mediating protein-protein interactions. The first-generation terphenyl scaffold, with a 3,2′,2”-substitution pattern, is able to successfully mimic key Helix residues and disrupt therapeutically relevant interactions, including the Bcl-X(L)-Bak and the p53-hDM2 (human double minute 2) interactions that are implicated in cancer. The second- and third-generation scaffolds have resulted in greater synthetic accessibility and more drug-like character in these molecules.

  • hydrophobic side chain interactions in a family of dimeric amide foldamers potential Alpha Helix mimetics
    Tetrahedron Letters, 2011
    Co-Authors: Oleg V Kulikov, Andrew D Hamilton, Christopher D Incarvito

    Abstract:

    Abstract A series of new AlphaHelix mimetics based on a benzamide scaffold and potentially able to disrupt protein-protein interactions have been synthesized and characterized by X-ray analysis. Inspection of the solid state structures of aromatic amide dimers confirmed that the molecules adopt a curved conformation with intramolecular H-bonding between the amide NH and the alkoxy oxygen of the neighboring aromatic fragment (dNH…O ∼ 2 A). Adjacent dimer molecules are prone to form supramolecular assemblies due to both hydrophobic alkyl side-chain/side-chain interactions and intermolecular H-bonding.

Neville R Kallenbach – 2nd expert on this subject based on the ideXlab platform

  • Structure of a C-Terminal .Alpha.-Helix Cap in a Synthetic Peptide
    Journal of the American Chemical Society, 1994
    Co-Authors: Hongxing X. Zhou, David E. Wemmer, Neville R Kallenbach

    Abstract:

    We report here a novel C-terminal capping structure in a peptide Helix, in which the NH of the side chain of asparagine forms an H-bond with the Helix main chain CO four residues away. The backbone forms a local 3[sub 10] Helix at the C-terminus, with the side chain contributing an additional H-bonded loop. This structure reveals formation of H-bonds by the side chain and main chain of a single residue that serve as a fundamental signal at the C-terminus of helices. The structure formed in this way blocks continuation of the [Alpha]Helix, hence providing a stronger C-termination signal than Pro 19, as seen in the relative CD values. 12 refs., 2 figs., 1 tab.

  • Alpha Helix stabilization by natural and unnatural amino acids with alkyl side chains
    Proceedings of the National Academy of Sciences of the United States of America, 1991
    Co-Authors: John C Sherman, A Chen, Neville R Kallenbach

    Abstract:

    Abstract
    Knowledge of the role of individual side chains in forming different secondary structures such as the AlphaHelix would be useful for prediction of protein structure from sequence or de novo protein design. Experimental and theoretical studies on natural and synthetic peptides and proteins indicate that individual side chains differ in their Helix-forming potential. Four aliphatic side chains occur in the standard complement of amino acids: alanine and leucine are Helix stabilizing, whereas isoleucine and valine are weakly destabilizing. We have synthesized a series of helical peptides containing unnatural aliphatic side chains having two to four carbons to explore some of the factors involved in AlphaHelix stabilization and the basis for selection of the natural set. We find that linear side chains with two, three, or four carbons are as strongly Helix stabilizing as the single methyl in alanine and that all linear side chains are stronger Helix promoters than leucine. In addition, a t-butyl side chain is significantly more Helix destabilizing than the sec-butyl side chain of isoleucine, the isopropyl side chain of valine, or even the unrestricted side chain of glycine. These results provide experimental evidence that restriction in conformational freedom of a side chain imposed by AlphaHelix formation is a major component of the role of a side chain in stabilizing helical structure.

V Haridas – 3rd expert on this subject based on the ideXlab platform

  • from peptides to non peptide Alpha Helix inducers and mimetics
    European Journal of Organic Chemistry, 2009
    Co-Authors: V Haridas

    Abstract:

    Helix mimetics are good models for investigating the theories of protein folding and also act as good affinity ligands for therapeutic applications due to their biostability and better blood-brain barrier crossing ability. The Helix mimetics display the same spatial and temporal orientation with respect to the amino acid side-chains of Alpha Helix part of the protein, which are involved in protein–protein interactions. The designed nonpeptidic molecules with substituents at the appropriate positions on the scaffold can mimic the amino acid side-chains of a fully folded Alpha Helix and can competitively bind with the target protein, thus acting as possible therapeutic agents. This was illustrated with examples like p53/MDM2, CD81/CV E2, Bcl-xL/Bak, gp-41, and others, with therapeutic relevance. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

  • From Peptides to Non‐Peptide AlphaHelix Inducers and Mimetics
    European Journal of Organic Chemistry, 2009
    Co-Authors: V Haridas

    Abstract:

    Helix mimetics are good models for investigating the theories of protein folding and also act as good affinity ligands for therapeutic applications due to their biostability and better blood-brain barrier crossing ability. The Helix mimetics display the same spatial and temporal orientation with respect to the amino acid side-chains of Alpha Helix part of the protein, which are involved in protein–protein interactions. The designed nonpeptidic molecules with substituents at the appropriate positions on the scaffold can mimic the amino acid side-chains of a fully folded Alpha Helix and can competitively bind with the target protein, thus acting as possible therapeutic agents. This was illustrated with examples like p53/MDM2, CD81/CV E2, Bcl-xL/Bak, gp-41, and others, with therapeutic relevance. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)